Edema Score Research Articles

Targeting inflammation and redox perturbations by lisinopril mitigates Freund's adjuvant-induced arthritis in rats: role of JAK-2/STAT-3/RANKL axis, MMPs, and VEGF.

Cardiovascular disorders are major complications of rheumatoid arthritis (RA). Hence, finding effective agents that can target RA progression and its cardiovascular consequences is demanding. The present work aimed to explore the potential of lisinopril, an angiotensin-converting enzyme inhibitor, to mitigate adjuvant's-induced arthritis with emphasis on the pro-inflammatory signals, articular degradation cues, and angiogenesis alongside JAK-2/STAT-3 and Nrf2/HO-1 pathways. Lisinopril (10mg/kg/day) was administered by oral gavage for 3weeks and thetarget signals were examined by biochemical assays, ELISA, histopathology, immunoblotting, and immunohistochemistry. Lisinopril attenuated the progression of arthritis as proven by lowering paw edema, arthritic index, and gait scores alongside diminishing the immune-cell infiltration/aberrant histopathology in the dorsal pouch lining. These favorable actions were associated with curtailing the production of inflammatory cytokines (TNF-α, IL-6, IL-1β, and IL-17) and the pro-inflammatory angiotensin II alongside upregulating the anti-inflammatory angiotensin-(1-7) in the hind paw of arthritic rats. At the molecular level, lisinopril inhibited the upstream JAK-2/STAT-3 pathway by downregulating the protein expression of p-JAK-2/total JAK-2 and p-STAT-3/total STAT-3 ratio and the nuclear levels of NF-κBp65. Meanwhile, lisinopril curbed the downstream cartilage degradation signals matrix metalloproteinases (MMP-3 and MMP-9) and the bone erosion cue RANKL. Equally important, the protein expression of the angiogenesis signal VEGF was downregulated in the hind paw/dorsal lining. With respect to oxidative stress, lisinopril suppressed the paw lipid peroxides and boosted GSH and Nrf-2/HO-1 pathway. Lisinopril attenuated adjuvant-induced arthritis via inhibition of inflammation, articular degradation cues, and angiogenesis.

Efficacy and safety of micronized purified flavonoid fractions for the treatment of postoperative hemorrhoid complications: A systematic review and meta-analysis

Hemorrhoids, a common anorectal disease, seriously affects patients' quality of life. Micronized purified flavonoid fractions (MPFF) have been shown to improve hemorrhoid symptoms. To evaluate the efficacy and safety of MPFF in treating postoperative hemorrhoid complications. A systematic review and meta-analysis of existing literature on natural compounds for treating postoperative complications of hemorrhoids. A literature search was conducted using five databases, namely PubMed, WanFang, CNKI, Embase, and the Cochrane Library, to identify randomized controlled trials (RCTs) on the effects of MPFF treatment on hemorrhoids. Stata 15.1 and Revman 15.4 were used to assess the data, while subgroup and sensitivity analyses were performed to evaluate potential heterogeneity, and trial sequential analysis (TSA) and Egger test were used to evaluate the reliability of each trial. A total of 22 RCTs, including 2,335 participants were included in the analysis. MPFF improved the clinical efficacy of post-hemorrhoidectomy and reduced the bleeding rate, pain score, and edema score, although no substantial effect on adverse reactions was reported. Subgroup analyses showed a significant reduction in pain score and bleeding rate in trials with duration of 4-10 days and an improvement in clinical efficacy. Treatment for ≥ 10 days significantly improved the edema score; a dosage range of 1,800-2,700 mg/day of MPFF significantly reduced edema and pain scores, whereas < 1,800 mg/day significantly improved clinical efficacy. Based on searching the relevant literatures, this is the first meta-analysis on MPFF treatment of postoperative hemorrhoid complications. Our findings, validated by TSA, suggest that MPFF is safe and effective in reducing postoperative hemorrhoid complications, and that dose and duration are key factors in its efficacy, as illustrated by subgroup analysis. However, due to the small sample size, the standardized treatment regimen of MPFF could not be obtained; therefore, further research is warranted.

Imaging-based indices combining disease severity and time from disease onset to predict COVID-19 mortality: A cohort study.

COVID-19 prognostic factors include age, sex, comorbidities, laboratory and imaging findings, and time from symptom onset to seeking care. The study aim was to evaluate indices combining disease severity measures and time from disease onset to predict mortality of COVID-19 patients admitted to the emergency department (ED). All consecutive COVID-19 patients who underwent both computed tomography (CT) and chest X-ray (CXR) at ED presentation between 27/02/2020 and 13/03/2020 were included. CT visual score of disease extension and CXR Radiographic Assessment of Lung Edema (RALE) score were collected. The CT- and CXR-based scores, C-reactive protein (CRP), and oxygen saturation levels (sO2) were separately combined with time from symptom onset to ED presentation to obtain severity/time indices. Multivariable regression age- and sex-adjusted models without and with severity/time indices were compared. For CXR-RALE, the models were tested in a validation cohort. Of the 308 included patients, 55 (17.9%) died. In multivariable logistic age- and sex-adjusted models for death at 30 days, severity/time indices showed good discrimination ability, higher for imaging than for laboratory measures (AUCCT = 0.92, AUCCXR = 0.90, AUCCRP = 0.88, AUCsO2 = 0.88). AUCCXR was lower in the validation cohort (0.79). The models including severity/time indices performed slightly better than models including measures of disease severity not combined with time and those including the Charlson Comorbidity Index, except for CRP-based models. Time from symptom onset to ED admission is a strong prognostic factor and provides added value to the interpretation of imaging and laboratory findings at ED presentation.

MRI characteristics of breast edema for assessing axillary lymph node burden in early-stage breast cancer: a retrospective bicentric study.

To investigate whether breast edema characteristics at preoperative T2-weighted imaging (T2WI) could help evaluate axillary lymph node (ALN) burden in patients with early-stage breast cancer. This retrospective study included women with clinical T1 and T2 stage breast cancer and preoperative MRI examination in two independent cohorts from May 2014 to December 2020. Low (< 3 LNs+) and high (≥ 3 LNs+) pathological ALN (pALN) burden were recorded as endpoint. Breast edema score (BES) was evaluated at T2WI. Univariable and multivariable analyses were performed by the logistic regression model. The added predictive value of BES was examined utilizing the area under the curve (AUC), net reclassification improvement (NRI), and integrated discrimination improvement (IDI). A total of 1092 patients were included in this study. BES was identified as the independent predictor of pALN burden in primary (n = 677) and validation (n = 415) cohorts. The analysis using MRI-ALN status showed that BES significantly improved the predictive performance of pALN burden (AUC: 0.65 vs 0.71, p < 0.001; IDI = 0.045, p < 0.001; continuous NRI = 0.159, p = 0.050). These results were confirmed in the validation cohort (AUC: 0.64 vs 0.69, p = 0.009; IDI = 0.050, p < 0.001; continuous NRI = 0.213, p = 0.047). Furthermore, BES was positively correlated with biologically invasive clinicopathological factors (p < 0.05). In individuals with early-stage breast cancer, preoperative MRI characteristics of breast edema could be a promising predictor for pALN burden, which may aid in treatment planning. • In this retrospective study of 1092 patients with early-stage breast cancer from two cohorts, the MRI characteristic of breast edema has independent and additive predictive value for assessing axillary lymph node burden. • Breast edema characteristics at T2WI positively correlated with biologically invasive clinicopathological factors, which may be useful for preoperative diagnosis and treatment planning for individual patients with breast cancer.

What Is the Optimal Speed of correction of the Hyperosmolar Hyperglycemic State in Diabetic Ketoacidosis? An Observational Cohort Study of U.S. Intensive Care Patients

ObjectiveThe international guidelines for the treatment of diabetic ketoacidosis (DKA) advise against rapid changes in osmolarity and glucose; however, the optimal rates of correction are unknown. We aimed to evaluate the rates of change in tonicity and glucose level in intensive care patients with DKA and their relationship with mortality and altered mental status. MethodsThis is an observational cohort study using 2 publicly available databases of U.S. intensive care patients (Medical Information Mart for Intensive Care-IV and Electronic Intensive Care Unit), evaluating adults with DKA and associated hyperosmolarity (baseline Osm ≥300 mOsm/L). The primary outcome was hospital mortality. The secondary neurologic outcome used a composite of diagnosed cerebral edema or Glasgow Coma Scale score of ≤12. Multivariable regression models were used to control for confounding factors. ResultsOn adjusted analysis, patients who underwent the most rapid correction of up to approximately 3 mmol/L/hour in tonicity had reduced mortality (n = 2307; odds ratio [OR], 0.21; overall P < .001) and adverse neurologic outcomes (OR, 0.44; P < .001). Faster correction of glucose levels up to 5 mmol/L/hour (90 mg/dL/hour) was associated with improvements in mortality (n = 2361; OR, 0.24; P = .020) and adverse neurologic events (OR, 0.52; P = .046). The number of patients corrected significantly faster than these rates was low. A maximal hourly rate of correction between 2 and 5 mmol/L for tonicity was associated with the lowest mortality rate on adjusted analysis. ConclusionBased on large-volume observational data, relatively rapid correction of tonicity and glucose level was associated with lower mortality and more favorable neurologic outcomes. Avoiding a maximum hourly rate of correction of tonicity >5 mmol/L may be advisable.

Predictive Factors of Functional Outcome in World Federation of Neurosurgical Societies Grade V Subarachnoid Hemorrhage

Patients with World Federation of Neurosurgical Societies (WFNS) grade V subarachnoid hemorrhage (SAH) frequently have poor outcomes. The current understanding of the predictors of functional outcome only in WFNS grade V SAH is limited. Patients with WFNS grade V SAH were retrospectively analyzed between April 2008 and August 2019. Surgical treatment is commonly delayed until clinical improvement is observed using a less aggressive approach. Clinical and radiologic data on admission were assessed, and disease-related characteristics were compared between patients with favorable outcomes (modified Rankin Scale score 0-3) and those with unfavorable outcomes (modified Rankin Scale score 4-6). A total of 144 patients were included, and 22 patients (15.3%) achieved favorable outcomes, whereas 122 patients (84.7%) had unfavorable outcomes. Surgical aneurysm repair was performed in all patients with favorable outcomes and in 21.3% of those with unfavorable outcomes. Multivariate analysis showed that Glasgow Coma Scale score of 3, high-grade Early Brain Edema Score, absence of bilaterally light reflex and neurologic improvement, and hypertension were significantly associatedwith unfavorable outcomes (odds ratio [OR], 9.54, P= 0.03; OR, 5.37, P= 0.04; OR, 11.80, P= 0.009; OR, 0.14, P= 0.02 and OR, 6.53, P= 0.04, respectively). The final outcome of patients with WFNS grade V SAH was still poor and highly predicted by Glasgow Coma Scale score of 3, high-grade Early Brain Edema Score, absence of bilaterally light reflex and neurologic improvement, and a history of hypertension. The efficacy of aggressive surgical treatment for these patients remains controversial, and the indications should be clearly defined in patients with desolate clinical status on admission.

Using Artificial Intelligence to Establish Chest X-Ray Image Recognition Model to Assist Crucial Diagnosis in Elder Patients With Dyspnea.

Pneumonia and pulmonary edema are the most common causes of acute respiratory failure in emergency and intensive care. Airway maintenance and heart function preservation are two foundations for resuscitation. Laboratory examinations have been utilized for clinicians to early differentiate pneumonia and pulmonary edema; however, none can provide results as prompt as radiology examinations, such as portable chest X-ray (CXR), which can quickly deliver results without mobilizing patients. However, similar features between pneumonia and pulmonary edema are found in CXR. It remains challenging for Emergency Department (ED) physicians to make immediate decisions as radiologists cannot be on-site all the time and provide support. Thus, Accurate interpretation of images remains challenging in the emergency setting. References have shown that deep convolutional neural networks (CNN) have a high sensitivity in CXR readings. In this retrospective study, we collected the CXR images of patients over 65 hospitalized with pneumonia or pulmonary edema diagnosis between 2016 and 2020. After using the ICD-10 codes to select qualified patient records and removing the duplicated ones, we used keywords to label the image reports found in the electronic medical record (EMR) system. After that, we categorized their CXR images into five categories: positive correlation, negative correlation, no correlation, low correlation, and high correlation. Subcategorization was also performed to better differentiate characteristics. We applied six experiments includes the crop interference and non-interference categories by GoogLeNet and applied three times of validations. In our best model, the F1 scores for pneumonia and pulmonary edema are 0.835 and 0.829, respectively; accuracy rate: 83.2%, Recall rate: 83.2%, positive predictive value: 83.3%, and F1 Score: 0.832. After the validation, the best accuracy rate of our model can reach up to 73%. The model has a high negative predictive value of excluding pulmonary edema, meaning the CXR shows no sign of pulmonary edema. At the time, there was a high positive predictive value in pneumonia. In that way, we could use it as a clinical decision support (CDS) system to rule out pulmonary edema and rule in pneumonia contributing to the critical care of the elderly.

Ventilatory Ratio Is a Valuable Prognostic Indicator in an Observational Cohort of Patients With ARDS.

How indices specific to respiratory compromise contribute to prognostication in patients with ARDS is not well characterized in general clinical populations. The primary objective of this study was to identify variables specific to respiratory failure that might add prognostic value to indicators of systemic illness severity in an observational cohort of subjects with ARDS. Fifty subjects with ARDS were enrolled in a single-center, prospective, observational cohort. We tested the contribution of respiratory variables (oxygenation index, ventilatory ratio [VR], and the radiographic assessment of lung edema score) to logistic regression models of 28-d mortality adjusted for indicators of systemic illness severity (the Acute Physiology and Chronic Health Evaluation [APACHE] III score or severity of shock as measured by the number of vasopressors required at baseline) using likelihood ratio testing. We also compared a model utilizing APACHE III with one including baseline number of vasopressors by comparing the area under the receiver operating curve (AUROC). VR significantly improved model performance by likelihood ratio testing when added to APACHE III (P = .036) or the number of vasopressors at baseline (P = .01). Number of vasopressors required at baseline had similar prognostic discrimination to the APACHE III. A model including the number of vasopressors and VR (AUROC 0.77 [95% CI 0.64-0.90]) was comparable to a model including APACHE III and VR (AUROC 0.81 [95% CI 0.68-0.93]; P for comparison = .58.). In this observational cohort of subjects with ARDS, the VR significantly improved discrimination for mortality when combined with indicators of severe systemic illness. The number of vasopressors required at baseline and APACHE III had similar discrimination for mortality when combined with VR. VR is easily obtained at the bedside and offers promise for clinical prognostication.

Pentoxifylline reduces post-breeding uterine fluid accumulation in older embryo donor mares and may enhance embryo recovery

Most donor mares in embryo transfer programs have impaired uterine clearance due to uterine and cervical problems. In addition, repeated breeding cycles, gynecological procedures, and embryo flushing make mares prone to endometritis. Anecdotally, pentoxifylline, an anti-inflammatory, has been used in mares to enhance blood flow in the reproductive tract and reduce uterine inflammation. However, this has not been critically studied. This study aimed to assess the post-breeding inflammatory response and embryo recovery of subfertile donor mares treated with pentoxifylline. This study hypothesized that pentoxifylline supplementation mitigates the post-breeding inflammatory response in embryo donor mares. Forty-two estrous cycles of seven embryo donor mares (16±3.7years old; 13±3years donating embryos) were completed in the study. In the first two cycles, mares received pentoxifylline (17mg/kg/day) given in 50mL of Broodmare-Plus® (Botupharma), the two subsequent cycles served as control, and in the last two cycles, mares received 50mL of Broodmare®. Mares were monitored daily, and then once a preovulatory follicle was detected, ovulation was induced with deslorelin (1mg, i.m.). Immediately before (0h), 24, 48, and 72h post-breeding mares had transrectal ultrasonography performed to determine ovulation, quantify uterine edema and intrauterine fluid accumulation (IUF). At similar timepoints, uterine cytology was collected, stained with Diff-Quik®, and polymorphous nuclear cells were counted in ten hpf. Embryo collections were performed eight days after ovulation, and mares receivedan injection of 5mg of dinoprost (i.m., Lutalyse, Zoetis, USA) to return to estrus. Statistical analyses were performed with Graph Prisma (San Diego, CA). Neutrophil counts were analyzed with ANOVA repeated measures and Tukey's as post-hoc. Edema scores and intrauterine fluid accumulation were analyzed with Kruskal-Wallis and Dunn's post-hoc. Embryo recovery rates were evaluated with Fisher's test. There was an effect of time for neutrophil counts in the washout cycle (P=0.032) but not in the other two groups (P>0.05). Neutrophil counts didn't differ across groups (P>0.05). Edema scores had effects of time (P=0.046) but no effects of group (P>0.05). Similarly, there was an effect of time (P=0.038) for IUF, and mares receiving pentoxifylline had reduced post-breeding IUF in comparison with washout cycles (P=0.034) but not different than the group receiving just Broodmare® (P>0.05). Embryo recovery was not different across groups (P>0.05) but remarkably different as follows: washout cycle was 29% (4/14); Broodmare® was 36% (5/14), and pentoxifylline (Broodmare-Plus®) was 57% (8/14). Mares in the study were subfertile older mares used as embryo donors for multiple years, thus, justifying the low embryo recovery for the cycles with no pentoxifylline. In conclusion, supplementation with pentoxifylline may be an alternative to improve the post-breeding uterine clearance. It may enhance embryo recovery in mares serving as donors for multiple years; however, this remains to be confirmed with a larger group number of mares.

Uterine inflammatory response after misoprostol during estrus and diestrus in commercial embryo donor mares

Uterine tube obstruction is the leading cause of unexplained subfertility in mares. Over the years, numerous techniques were developed to unblock uterine tubes with variable success. In recent years, the administration of misoprostol, a synthetic analog of prostaglandin E1, in the uterus, has regained popularity in equine practice. However, there have been some concerns regarding an exacerbated post-infusion uterine inflammatory response to misoprostol; nonetheless, this has yet to be critically studied. In addition, debate exists when mares should receive misoprostol. This study aimed to determine the uterine inflammatory response in mares after infusion with misoprostol during estrus or diestrus. We hypothesized that misoprostol infusion induces a greater inflammatory response than sham infusion; similarly, diestrus results in a greater inflammatory response than estrus. Forty-four estrous cycles of light breed mares (n=11) were sequentially randomly assigned to receive misoprostol or sham infusion during estrus and diestrus. The misoprostol and sham infusions were performed by directing a flexible pipette (Minitube, Germany) deep into each uterine horns, which received 200mcg of misoprostol diluted in 3 mL of Lactate Ringer's Solution (LRS), whereas the sham inoculation consisted of 3 mL of LRS. The cycles assigned for estrus treatment received it when preovulatory follicles ranged from 28-32 mm, and diestrus cycles were treated eight days post-ovulation. The day after each infusion, mares had uterine lavage performedwith LRS. Uterine edema and intrauterine fluid accumulation were performed by transrectal ultrasonography immediately before (0h), 24, 48, and 72 h after treatments. At similar time points, uterine cytology samples were harvested to count the number of neutrophils in a high-power field (400 ×). Ovulation was hastened with deslorelin (1mg, i.m.) during estrus or the subsequent estrus after diestrus infusion. Mares received 5 mg of dinoprost (i.m.) 24 h after infusion in estrus and diestrus. Statistical analyses were performed with Graph Prisma. Neutrophil counts were analyzed with ANOVA repeated measures and Tukey's as post-hoc. Edema scores and intrauterine fluid accumulation were analyzed with Kruskal-Wallis and Dunn's post-hoc. Embryo recovery rates were evaluated with Fisher's test. There were effects of time (P=0.04) but no effects of group (P=0.96), or stage of the estrous cycle (P=0.26), or interaction between group and time for edema scores (P=0.97). Similarly, there were effects of time (P=0.03) but no effects of group (P=0.32), stage of the estrous cycle (P=0.86), or interactions between group and time or stage of the estrous cycle for neutrophil counts (P=0.87). Uterine fluid scores did not change over time (P=0.39), groups (P=0.22), or stage of the estrous cycle (P=0.77). Embryo recovery was similar for estrus (Misoprostol 46% vs. sham 46%) vs. diestrus (Misoprostol 67% vs. sham 46%) (P>0.05). In conclusion, 200 mcg of misoprostol bilateral administration did not exacerbate uterine inflammation in mares.

5-Aminolevulinic acid has the potential to prevent bladder dysfunction in cyclophosphamide-induced hemorrhagic cystitis.

To investigate the effects of pretreatment with 5-aminolevulinic acid hydrochloride combined with sodium ferrous citrate on bladder dysfunction in cyclophosphamide-induced hemorrhagic cystitis in rats. Male Wistar rats (340-460 g) were pretreated with vehicle or with 5-aminolevulinic acid hydrochloride combined with sodium ferrous citrate (100/157 or 300/471 mg/kg/day, po) once daily for 7 days before cystometry. Saline or cyclophosphamide (150 mg/kg, ip) was administered 2 days before cystometry. Cystometry was performed under urethane anesthesia (0.8 g/kg, ip) via a catheter inserted into the bladder. After cystometry, bladder tissues were collected to perform hematoxylin and eosin staining for pathological evaluation (neutrophil infiltration, edema, and bleeding scores), and for enzyme-linked immunosorbent assay and real-time polymerase chain reaction for investigating tissue levels of myeloperoxidase, and mRNA levels of haem oxygenase-1 as a cytoprotective molecule. Compared to controls, cyclophosphamide induced a shorter intercontraction interval, lower bladder compliance, increased number of non-voiding contractions, and increased pathological scores and myeloperoxidase expression in the bladder. Pretreatment with 5-aminolevulinic acid hydrochloride combined with sodium ferrous citrate (300/471 mg/kg/day) significantly improved cyclophosphamide-induced intercontraction interval shortening and increases in number of non-voiding contractions and neutrophil infiltration/bleeding scores and enhanced haem oxygenase-1 expression in the bladder. In addition, cyclophosphamide-induced decreases in bladder compliance and increases in myeloperoxidase were not detected with 5-aminolevulinic acid hydrochloride combined with sodium ferrous citrate pretreatment. Pretreatment with 5-aminolevulinic acid expects protective effects on bladder dysfunction in cyclophosphamide-induced hemorrhagic cystitis by improving inflammatory changes in bladder tissues perhaps via up-regulation of haem oxygenase-1.

Clinical Outcome Discrimination in Pediatric ARDS by Chest Radiograph Severity Scoring.

Background There is no accurate radiological measurement to estimate the severity of pediatrics acute respiratory distress syndrome (PARDS). We validated the effectiveness of an adult radiographic assessment of lung edema (RALE) score in PARDS. Aim To assess the severity and prognosis of PARDS based on a chest radiograph (CXR) RALE scoring method. Methods Pediatric Acute Lung Injury Consensus Conference (PALICC) criteria were used to diagnose PARDS. General demographics, pulmonary complications, and 28‐day mortality of the patients were recorded. Subgroups were compared by prognosis (survive and death) and etiology (infection and noninfection). Two observers calculated RALE independently. Each quadrant of CXR was scored by consolidation scores 0 (none alveolar opacity), 1 (extent <25%), 2 (extent 25%–50%), 3 (50%–75%), and 4 (>75%) and density scores 1 (hazy), 2 (moderate), and 3 (dense). Quadrant score equals consolidation score times density score. Total score equals to the sum of four quadrants scores. The ROC curve and survival curve were established, and the optimal cutoff score for discrimination prognosis was set. Results 116 PARDS (72 boys and 44 girls) and 463 CXRs were enrolled. The median age was 25 months (5 months, 60.8 months) and with a mortality of 37.9% (44/116). The agreement between two independent observers was excellent (ICC = 0.98, 95% CI: 0.97–0.99). Day 3 score was independently associated with better survival (p < 0.001). The area under the curve of ROC was 0.773 (95% CI: 0.709–0.838). The cutoff score was 21 (sensitivity 71.7%, specificity 76.5%), and the hazard ratio (HR) was 9.268 (95% CI: 1.257–68.320). The pulmonary complication showed an HR of 3.678 (95% CI: 1.174–11.521) for the discrimination. Conclusion CXR RALE score can be used in PARDS for discriminating the prognosis and has a better agreement among radiologist and pediatrician. PARDS with pulmonary complications, day 3 score whether greater than 21 points, have a better predictive effectiveness.

Chest Radiograph Severity Scores, Comorbidity Prevalence, and Outcomes of Patients with Coronavirus Disease Treated at the King Abdullah University Hospital in Jordan: A Retrospective Study.

IntroductionHospitalized patients with coronavirus disease (COVID-19) often undergo chest x-ray (CXR). Utilizing CXR findings could reduce the cost of COVID-19 treatment and the resultant pressure on the Jordanian healthcare system.MethodsWe evaluated the association between the CXR severity score, based on the Radiographic Assessment of Lung Edema (RALE) scoring system, and outcomes of patients with COVID-19. The main objective of this work is to assess the role of the RALE scoring system in predicting in-hospital mortality and clinical outcomes of patients with COVID-19. Adults with a positive severe acute respiratory syndrome COVID-19 two reverse-transcription polymerase chain reaction test results and a baseline CXR image, obtained in November 2020, were included. The RALE severity scores were calculated by expert radiologists and categorized as normal, mild, moderate, and severe. Chi-square tests and multivariable logistic regression were used to assess the association between the severity category and admission location and clinical characteristics.ResultsBased on the multivariable regression analysis, it has been found that male sex, hypertension, and the RALE severity score were significantly associated with in-hospital mortality. The baseline RALE severity score was associated with the need for critical care (P<0.001), in-hospital mortality (P<0.001), and the admission location (P=0.002).DiscussionThe utilization of RALE severity scores helps to predict clinical outcomes and promote prudent use of resources during the COVID-19 pandemic.

Transcriptional Landscape Established by the Euchromatic Histone‐lysine N‐methyltransferase Pathway During Pancreas Ontogenesis and Pancreatitis

The Euchromatic Histone‐lysine N‐Methyltransferase 1/2 (EHMT1/2) complex, responsible for catalyzing mono‐ and di‐methylation of histone H3K9, has emerged as key regulator of embryogenesis and carcinogenesis. We have recently shown that EHMT2 inactivation antagonizes oncogenic KRAS‐mediated pancreatic cancer initiation and promotion by altering growth and immune gene expression networks. The current study unravels the transcriptional landscape regulated by EHMT2 during pancreatic development and acute pancreatitis. We performed conditional knockout of EHMT2 in the pancreas using the Pdx1‐Cre model, comparing perinatal (10‐day‐old) vs. young adult mice (4‐week‐old). Notably, despite carrying EHMT2 inactivation, both the whole animal and pancreas develop normally through adulthood. The transcriptional landscape resulting from EHMT2 inactivation, however, is different in perinatal mice from young adults, suggesting that this epigenomic regulator plays a role in modulating distinct gene networks during the development of this organ. Congruent with a role for EHMT2 in gene silencing, we show that its inactivation in both life stages primarily resulted in gene expression signatures dominated by upregulated transcripts. Notably, among these genes, we find pancreas‐specific clusters, including those encoding zymogen granules, during the transition to young adult, suggesting that EHMT2 facilitates acinar cell‐fate decisions. DEGs from young adults with EHMT2 loss displayed prominent activation of TP53 signaling‐related and DNA damage response gene networks that were not present in the perinatal cohort, demonstrating that cell cycle arrest accompanies this differentiation event. We also find de‐repression of genes that participate in early endodermal development, metabolism, and inflammation. Studies on acute pancreatitis, induced by repeated injections of the CCK‐agonist peptide, caerulein, show that EHMT2 inactivation results in more severe disease compared to that in controls, as measured by histological scoring of edema, inflammatory cell infiltrate, and necrosis. More importantly, and congruent with our histological assessment, EHMT2 inactivation in acinar epithelial cells regulates the expression of key inflammation‐associated genes that reprograms the non‐epithelial responses to pancreatitis. Digital cytology analysis demonstrated that the transcriptional landscape resulting from EHMT2 inactivation triggers a more aggressive inflammatory response for the pancreas. This data demonstrates that, although not critical to development of the organ, EHMT2 is involved in pancreas‐specific gene expression. Lastly, during pancreatitis, EHMT2 behaves as an important regulator of inflammation, extending our knowledge of epigenomic mechanisms underlying development, homeostasis, and diseases of the pancreas.

Evaluation of Antiarthritic and Antinociceptive Effects of Cedrol in a Rat Model of Arthritis.

Pharmacological studies revealed that cedrol, a natural sesquiterpene, has antioxidant, anti-inflammatory, and analgesic properties. This study is aimed at evaluating the potential antiarthritic activity of cedrol in a rat experimental model of arthritis induced by using complete Freund's adjuvant (CFA). Arthritis was induced in Wistar rats by CFA (0.1 ml) injection. Cedrol (10 and 20 mg/kg) and indomethacin (5 mg/kg) were orally administered from day one and continued for 21 days. The antiarthritic activity was assessed through mechanical allodynia and thermal hyperalgesia responses, paw edema assessment, and arthritis scores. Serum TNF-α and IL-1β levels were measured for the evaluation of inflammation. Furthermore, serum oxidative stress markers, including malondialdehyde (MDA) and thiol levels, as well as superoxide dismutase (SOD) and glutathione peroxidase (GPx) activities, were also assessed. Oral administration of cedrol and indomethacin significantly decreased paw edema and arthritis score. Besides, cedrol and indomethacin significantly decreased pain responses. In the serum of the CFA group, TNF-α, IL-1β, and MDA were higher, while thiol and SOD and GPx were lower than the control group. Treatment by cedrol and indomethacin corrected the biochemical parameters in the serum. In this study, cedrol offers potential antiarthritic properties through its anti-inflammatory and antioxidant effects.

External COVID-19 Deep Learning Model Validation on ACR AI-LAB: It's a Brave New World.

PurposeDeploying external artificial intelligence (AI) models locally can be logistically challenging. We aimed to use the ACR AI-LAB software platform for local testing of a chest radiograph (CXR) algorithm for COVID-19 lung disease severity assessment.MethodsAn externally developed deep learning model for COVID-19 radiographic lung disease severity assessment was loaded into the AI-LAB platform at an independent academic medical center, which was separate from the institution in which the model was trained. The data set consisted of CXR images from 141 patients with reverse transcription-polymerase chain reaction–confirmed COVID-19, which were routed to AI-LAB for model inference. The model calculated a Pulmonary X-ray Severity (PXS) score for each image. This score was correlated with the average of a radiologist-based assessment of severity, the modified Radiographic Assessment of Lung Edema score, independently interpreted by three radiologists. The associations between the PXS score and patient admission and intubation or death were assessed.ResultsThe PXS score deployed in AI-LAB correlated with the radiologist-determined modified Radiographic Assessment of Lung Edema score (r = 0.80). PXS score was significantly higher in patients who were admitted (4.0 versus 1.3, P < .001) or intubated or died within 3 days (5.5 versus 3.3, P = .001).ConclusionsAI-LAB was successfully used to test an external COVID-19 CXR AI algorithm on local data with relative ease, showing generalizability of the PXS score model. For AI models to scale and be clinically useful, software tools that facilitate the local testing process, like the freely available AI-LAB, will be important to cross the AI implementation gap in health care systems.

Old targets, new strategy: Apigenin-7-O-β-d-(-6″-p-coumaroyl)-glucopyranoside prevents endothelial ferroptosis and alleviates intestinal ischemia-reperfusion injury through HO-1 and MAO-B inhibition

With the increasing morbidity and mortality, intestinal ischemia/reperfusion injury (IIRI) has attracted more and more attention, but there is no efficient therapeutics at present. Apigenin-7-O-β-D-(-6″-p-coumaroyl)-glucopyranoside (APG) is a new flavonoid glycoside isolated from Clematis tangutica that has strong antioxidant abilities in previous studies. However, the pharmacodynamic function and mechanism of APG on IIRI remain unknown. This study aimed to investigate the effects of APG on IIRI both in vivo and in vitro and identify the potential molecular mechanism. We found that APG could significantly improve intestinal edema and increase Chiu's score. MST analysis suggested that APG could specifically bind to heme oxygenase 1 (HO-1) and monoamine oxidase b (MAO-B). Simultaneously, APG could attenuate ROS generation and Fe2+ accumulation, maintain mitochondria function thus inhibit ferroptosis with a dose-dependent manner. Moreover, we used siRNA silencing technology to confirm that knocking down both HO-1 and MAO-B had a positive effect on intestine. In addition, we found the HO-1 and MAO-B inhibitors also could reduce endothelial cell loss and protect vascular endothelial after reperfusion. We demonstrate that APG plays a protective role on decreasing activation of HO-1 and MAO-B, attenuating IIRI-induced ROS generation and Fe2+ accumulation, maintaining mitochondria function thus inhibiting ferroptosis.

Anemia And Other Independent Predictors Of 30-day Readmissions In Heart Failure Patients: A Retrospective Study

<h3>Objectives</h3> To determine if there is an association between anemia and 30-day readmissions in patients with heart failure, and to identify other risk factors for 30-day readmissions in this group. <h3>Background</h3> : Anemia commonly occurs in patients with chronic heart failure, with a prevalence of up to 79%. It can be explained by the presence of comorbidities, chronic kidney disease, and differences in heart failure treatment. Anemia is likely associated with worse clinical outcomes in those patients because of a mismatch in oxygen supply and demand, increased resistance to erythropoietin, higher rates of left ventricular hypertrophy and fluid overload, and chronic inflammation. Findings associated with anemia in heart failure patients include symptoms, echocardiogram measurements, renal function, mortality, hospitalization rates and lengths of hospital stays. Few studies, however, have assessed the association of anemia with 30-day readmission rates in these patients. <h3>Methods</h3> : We conducted a retrospective chart review of patients with heart failure admitted to Ascension St John Hospital in Michigan from 1/1/2018 to 12/31/2019. Data were collected on demographics, comorbidities, laboratory testing during the index hospitalization, echocardiogram findings, and 30-day readmissions. Anemia was defined as hemoglobin less than 13 g/dL in males and hemoglobin less than 12 g/dL in females. Data were analyzed using Student's t-test, the χ2 test and logistic regression. <h3>Results</h3> : We reviewed 1250 patients with heart failure, 58.2% male, 52.6% non-white, mean age 68.2 ± 15.3 years. Of those patients, 24.2% (303/1250) were readmitted within 30 days; 55.5% of those readmissions were a result of cardiovascular disease. Anemia was noted in 62.2% of the patients (778/1250). From univariable analysis, the following factors were found to be associated with 30-day readmissions in heart failure patients: anemia (p = 0.008), female sex (p = 0.03), pulmonary edema (p = 0.013), hyponatremia (p = 0.005), atrial fibrillation or flutter (p = 0.04), hyperlipidemia (p = 0.042), antiarrhythmic medications (p < 0.0001), and Charlson Weighted Index of Comorbidity (CWIC) score (p < 0.0001). From multivariable analysis, heart failure patients who were readmitted within 30 days were more likely to be anemic (OR = 1.4, p = 0.029), hyponatremic (OR = 1.5, p = 0.007), have pulmonary edema on chest imaging during the index hospitalization (OR = 1.4, p = 0.033), prescribed antiarrhythmic medications (OR = 1.8, p = 0.002), and have higher CWIC scores (OR = 1.1, p = 0.001). <h3>Conclusions</h3> : In patients with heart failure, after controlling for other risk factors, anemic patients were 40% more likely to be readmitted within 30-days compared to non-anemic patients. Other independent predictors of 30-day readmissions included hyponatremia, pulmonary edema, antiarrhythmic medications, and CWIC score.

Role of chest radiography in COVID-19

OBJECTIVES: The objective of this study is to evaluate the clinical profile of coronavirus disease-2019 (COVID-19) patients admitted to our hospital and to correlate their chest radiographic patterns with disease severity. MATERIALS AND METHODS: We retrospectively reviewed 500 patients with COVID-19 confirmed by reverse transcription-polymerase chain reaction who had abnormal baseline chest X-rays (CXRs) at the time of hospital admission. CXRs were characterized based on the site and nature of the lesions. Disease severity was determined using the Radiographic Assessment of Lung Edema (RALE) score. RESULTS: Significant associations were found between (1) the lesion site and patient outcome (P &lt; 0.00001): patients with diffuse and basal infiltrates had high intensive care unit (ICU) admission rates (55.5% and 40%) and mortality rates (30.5% and 20%); (2) the nature of the lesion and patient outcome: patients with ground-glass opacities and consolidation had high mortality (20% and 18%, respectively); and (3) the RALE score and patient outcome: patients with a RALE score &gt;15 had higher ICU admission and mortality rates. CONCLUSIONS: The CXR distribution patterns helped to triage patients and predict outcomes.

Utility of a Pulmonary Oedema Score for Predicting the Need for Mechanical Ventilation in COVID-19 Patients in a General Hospital

BackgroundThe Radiographic Assessment of Lung Edema (RALE) score has been used to estimate the extent of pulmonary damage in patients with acute respiratory distress syndrome and might be useful in patients with COVID-19.Aim of the studyTo examine factors associated with the need for mechanical ventilation in hospitalized patients with a clinical diagnosis of COVID-19, and to estimate the predictive value of the RALE score.MethodsIn a series of patients admitted between April 14 and August 28, 2020, with a clinical diagnosis of COVID-19, we assessed lung involvement on the chest radiograph using the RALE score. We examined factors associated with the need for mechanical ventilation in bivariate and multivariate analysis. The area under the receiver operating curve (AUC) indicated the predictive value of the RALE score for need for mechanical ventilation.ResultsAmong 189 patients, 90 (48%) were judged to need mechanical ventilation, although only 60 were placed on a ventilator. The factors associated with the need for mechanical ventilation were a RALE score >6 points, age >50 years, and presence of chronic kidney disease. The AUC for the RALE score was 60.9% (95% CI 52.9–68.9), indicating it was an acceptable predictor of needing mechanical ventilation.ConclusionsA score for extent of pulmonary oedema on the plain chest radiograph was a useful predictor of the need for mechanical ventilation of hospitalized patients with COVID-19.